Trypanosoma cruzi is a parasitic hemoflagellate and is the causative agent of Chagas Disease. This parasitic disease constitutes a major health hazard to man in South and Central America and, thus far, no successful chemotherapeutic cure or immunological methods to prevent infection have been developed. Since both man and experimental animals can develop acquired resistance against acute infections of T. cruzi, the development of effective immunoprophylaxis for prevention and control of this parasite should be feasible with adequate knowledge. The latter will certainly include an understanding of the antiparasite immune responses and a clear distinction between those parasite antigens which may provide protection and those which might contribute to immuno pathological damage in the host. The ability to clearly identify and isolate or synthesize relevant parasite antigens would be of tremendous value in these areas. Accordingly, the major emphasis of the experiments proposed in this grant is directed toward the identification of relevant antigens on the surface of the parasite and development of methods for the procurement of these antigens in sufficient quantities to test their vaccination properties. Specifically, we plan to identify the dominant immunogenic surface proteins on the bloodstream form of the Peru strain of T. cruzi; (2) derive hybridoma cell lines for the production of monoclonal antibodies directed against these specific surface antigens; (3) determine whether monoclonal antibodies directed against a specific surface protein can confer protection to mice against an otherwise lethal inoculum of parasites. The results of these studies will allow us to identify those surface antigens which are potentially immunologically relevant. (4) construction of a library of recombinant cDNA plasmids which contains the entire sequence complexity of the poly(A+) mRNA of bloodstream trypomastigotes; (5) identify and isolate cDNA plasmids from this library which contain the coding sequences for the surface antigen genes. Once the desired gene sequences have been isolated, future studies should allow us to determine the feasibility of producing specific antigens in large amounts by use of recombinant DNA technology.